This is the Washington University School of Medicine Oral History Program. Oral History #55. This is June 7, 1982. I am Paul Anderson and I am speaking today with Dr. Francis Otto Schmitt. Dr. Schmitt was born in St. Louis November 23, 1903. He received a Bachelor’s degree from Washington University in 1924. Thereafter, for three years he was a graduate student in physiology under Dr. Joseph Erlanger here at the School of Medicine. It is this period of his life which is of particular interest to us here. Dr. Schmitt received a Ph.D. in physiology from Washington University in 1927. Thereafter, he was a National Research Council fellow in chemistry at the University of California at Berkeley, 1927-1928. He was at the University of London studying biochemistry in 1928-1929, and in Berlin at the Kaiser Wilhelm Institute in 1929. Dr. Schmitt returned to Washington University in 1929 as an assistant professor of Zoology. During the 1930s he advanced to become a full professor of zoology and in the 1940-1941 year head of the department.
In 1941 Dr. Schmitt joined the Massachusetts Institute of Technology. He has been associated with MIT since that time. He has been chairman of the department and presently he is Institute Professor Emeritus. In 1962 he founded the Neurosciences Research Program at MIT. This program functions as a center for theoretical research in many disciplines concerning the brain and its functions. He himself is recognized as a leading researcher in molecular biology.
To begin, Dr. Schmitt – first of all, did I make any gross errors in sketching out your life?
No, that was quite right.
Tell me briefly about your family here in St. Louis.
Well, I grew up on the south side. My mother was a very good scholar and was offered a four-year scholarship to a college when she graduated from high school. She preferred, however, not to take it in order to help her father, who was in a business in south St. Louis. She married my father, who was in a similar business at the time and Mr. Sinegar, who was her father, and my father, Otto Schmitt, [formed] a company called Sinegar and Schmitt. They bought a shop and living quarters over it at 3259 California Avenue in south St. Louis. And that served as their place of business when it was expanded to become a wholesale place and then a distributing center. It did very well, and as a young student I drove a truck to deliver materials. I would come home from school, from college, and have a route waiting for me and I’d come home frequently at seven or eight o’clock at night having finished the delivery route, which made me rather tired to study undergraduate material.
What kind of merchandise did Sinegar and Schmitt deal with?
Paint and wallpaper and decorators’ supplies and things like that. And when he went wholesale, he would buy the paper by the carload – that’s fifty thousand rolls – and they would always select that by going to New York and seeing all the different companies’ papers and then would select what he thought would be a good book. And his tastes were always right on the mark because they did quite well in it. So I grew up doing whatever I could to help in this, driving a truck, hoisting paper up in a storage room, and all kinds of things like that. When my mother died and my father continued to run the business, my sister and her son ran it for a period of years. My father then died at eighty-two of a massive stroke, so subsequently my sister decided to sell it and that was the end of the company.
That’s interesting for the business history of St. Louis, as well as concerning your career. When did you first decide to become a scientist rather than a businessman?
Oh, I knew since I was very, very small that I was to be a surgeon. I took the science courses in high school; I did the pre-medic course at the university. My father gave me a laboratory on the third floor of our place, where I had chemical reagents and did experiments up there. And enjoyed it. He gave me a microscope and I started playing with protozoa, etc., etc. So that I was just grooved in on science and I became at the university (in the college – that is, undergraduate), president of a student science organization. I was polarized that way, right from the beginning.
So you had a great deal of encouragement from your family?
Oh, yes. And my uncle was a physician. He assured my father that I would be an investigator and not a practitioner in all probability. Of course he proved to be quite right.
Why did he make that judgment?
His daughter – he had two daughters who received Ph.D.s, one in botany from Washington University – and she married another man who got his doctorate at Washington University. And so this uncle, Dr. Smith – he changed his name from Schmitt to Smith.
What was his first name?
Carl.
Carl. Carl Smith?
Yeah. He wanted very much to support my career in medicine and in science, in particular. And at all times [he] impressed my father with the fact that I should be allowed to continue in any kind of investigative work that I thought I would like to do. My father wanted me to be a surgeon and when I finally came to the medical school it was with the idea of getting an M.D. for him and a Ph.D. for me. But my senior professor at that time, Professor [Joseph] Erlanger, told my father that it would be an utter waste of three years of my time, precious time at that time particularly in growing up, to do anything clinical whatsoever. So my father said, “Well, he’s old enough to know what he wants to do, so perhaps he’ll do that.” And that saved me from being a surgeon. And it probably saved a lot of people who are walking around alive today because I decided not to be a surgeon.
Dr. Erlanger made this judgment upon your enrolling at the medical school?
Oh, no. When I got launched I was doing the regular medical students’ work, on top of which I was doing research. He observed what I was doing and I talked over with him the question of this double entendre to be a doctor and maybe even a surgeon, but also to be a scientist. And I think he was quite right to advise [me] to forget the clinical business.
So this conversation with Dr. Erlanger occurred when you first began to take your physiology course.
Oh, yes. While I was here.
That was one question that naturally came to me – that it wasn’t as usual then as it is now to have students doing graduate work in the sciences outside the medical curriculum. Is that true?
Well, I am an inveterate investigator. That’s what I lived for, in a sense. At that time, when I came, immediately he started me out. He had been working on shock during the First World War and had been closely involved in the influence of certain kinds of chemicals which produce shock, and certain other kinds of chemicals that tend to prevent it. So he put me on that right away and I started working on that in a big, big laboratory there up on the fourth floor of the South Building. And pretty soon, Dr. [George H.] Bishop saw what I was up to and felt that I just needed to get into a laboratory where I would do what I wanted to do and it wouldn’t be shock. So he got Dr. Erlanger to agree and I occupied a single room, not out there in the lab, but a single laboratory all my own. Then I really started in working on all kinds of things.
This was also the South Building?
Oh, yes. On the fourth floor, right in that group.
You’re describing a situation that perhaps couldn’t possibly exist now. Laboratory space is quite expensive; the contact between beginning students and senior professors is not nearly so full as you enjoyed. I see you nodding that I’m right in these assumptions.
Well, I was the only graduate student he had.
I see. None of the medical students decided to specialize in physiology as he had?
Well, there were medical students who worked somewhat in the laboratories, in the physiological laboratories, apart from the didactic work. But none of them were signed up, were registered in a graduate school as I was. There were not that many in all the medical school in 1924 that were literally graduate students at the same time that they were taking medical courses. I took all the medical courses the first two years.
I looked in the catalog that showed all the medical students formally enrolled and I didn’t see your name.
No, I wasn’t enrolled as an M.D. student. I was enrolled as a graduate student, but I took all those courses. And I could have switched. You see, I didn’t want formally to say, “I’m going to get an M.D. and I’m going to get a Ph.D.” I preferred not to say that, but on the other hand, I agreed to take the courses, many of which were not suited to me, to my needs; as Dr. [Robert J.] Terry who said of anatomy, said to me more than once – that human dissection as the medical students did in those days was surely not the kind of anatomy that suited my investigative career. And I agreed with him.
This was something that interests me because you’re saying that Dr. Terry had the foresight to see that in a way that gross anatomy was – its great days were about over. He could see that. He didn’t personally resist it?
It was stultifying, actually
He didn’t resist this trend?
He had little possibility of doing much about it, I feel. Another man who went – there were only three of us who went to the University for a degree before coming to the medical school. It was customary to come down after two years of premedical work, and George Seib, (spells) S-e-i-b, was another who did as I did, and he grew up in Anatomy under Terry. And Lawrence Goldman, who was a brilliant student, got into pediatric work, but died very early. At any rate, George is still alive and we talk frequently about anatomy. And Mildred Trotter is still alive and I talk with her about it. And I think we all agree that it was not a suitable thing for the kind of thing which now, in many large medical institutions, enrolls many people that are doing graduate work in biomedical subjects. Biochemistry long was that way; anatomy was not.
You’re referring, for example, to the research done in neuroanatomy?
Neuroanatomy was somewhat better, in my belief. Of course, we had a very special man who was very good. Still, it was a fairly routine kind of thing that a neurologist would need to know, if he were going to do any kind of neurology in his medical career. A wiring diagram – where did it go wrong, where is the lesion, and that sort of thing. It had very little in it of dynamics of neuroscience – none whatever. It was purely morphological – where is this nerve, and where is that nerve, and where does it come from, and where does it go?
If I may pursue a little further the relationship between the basic research sciences and the clinical sciences, I seem to recall that Dr. Evarts Graham was ultimately – whether he was this way to begin with or not I don’t know – of the belief that physiology was a very basic part of the training of a surgeon. In retrospect did you look back and say “Perhaps Dr. Erlanger was wrong”?
No, no, no. Because I knew Evarts Graham very well indeed. In Rome in 1932 at an international physiological congress which he attended along with his wife, Helen Graham, [he] sat on the side of a fountain in Constantine’s Garden and told me what he thought a surgeon ought to be thinking about and doing – [that] a surgeon who knows only how to cut, as it were, without an understanding of physiology and the whole picture, including pharmacology and all that, is not what he ought to be. There were people who thought that there were better surgeons in this institution than Evarts Graham. I knew that, but the fact remains that Evarts Graham was indeed the top man for very good reasons, not the least of which was that he inspired others to emulate him in learning physiology and so on. It was because of this flair that he had – he didn’t really do very much in investigation and published research and so on until years later.
He and his wife, Helen Graham, smoked constantly – cigarettes. I was a member of the National Academy of Sciences when in those days the National Academy held fall meetings off the campus [which was] in Washington, D. C., at the headquarters of the Academy. They went to different universities and it was the turn of Washington University. Our visit here was in November of – I’d have to think about what year it was – in the ’50s. At any rate, I was appointed to make arrangements out here because they knew I knew the way here. I did indeed make arrangements for the programs and that. And Dr. Graham there showed his experiments – read a paper on it – in which he was condensing cigarette smoke into the tar that it is and then painting that on the backs of mice and showing that it became malignant – and with overwhelming statistical evidence.
They had a very nice home at the junction of the Missouri and Mississippi Rivers. And we were invited – Herbert Gasser with all of us – for dinner. And neither of the Grahams were smoking. Evarts Graham was the first to take a lung out of a person successfully. Evarts died of lung cancer; the man whom he saved was at his funeral. He, in a sense, in the years that were granted him, after he realized what was going on, did everything he could in the way of investigation. And we all know now that he was right and it should have been done twenty years earlier.
That’s an interesting story. To go back to the question of the relationship of the clinicians and the basic researchers – were there any people who resented the kind of investment and money, or didn’t understand why medicine needed this kind of research?
I suppose so. I suppose so. I had no contact with such people. As far as I know, I was working only with people who were sympathetic to this kind of business.
Could you describe Dr. Erlanger’s laboratories – the kind of equipment, the kind of atmosphere?
Well, Dr. Erlanger was a superb lecturer. I know, because I was with the medical students and I saw what they did and I saw what I did. What we did was we sat there and listened. He had a person by the name of Elmer who used to help make demonstrations in the little anteroom and they’d wheel in the dog or the cat or whatever that the preparation had already been made [on] which he would then demonstrate. And we sat there understanding everything he said, or thought we did. And when we went home to write our notes, we didn’t know it as well as we thought. He had made it so clear. Well, I soon learned I’d better write my notes, nevertheless. At any rate, he was an excellent lecturer.
Tell me about Elmer. I’ve heard such a person alluded to.
Elmer – I haven’t the slightest notion what his last name was.
He was on the science department staff?
Oh, yes. Physiology department.
This was the person who helped him rig some of the [experiments]?
Oh, yes – whoever was lecturing – George Bishop or Artie [Arthur S.] Gilson or whoever was doing the lecture. If they were going to have a demonstration he would help them. He was expert at it; he knew where everything was. He’d cart in the thing and be right there to help the professor when the professor did something to the animal to show [that] the recorder would do whatever. And Elmer had to see that everything was working right. He was just a wonderful person that we all liked very much.
To complete the atmosphere, to look around from where the experiment was being conducted to the students – we can imagine students all very formally dressed?
Well, certainly as compared with today they were. We wouldn’t dream of appearing without a necktie and a jacket, but otherwise, there was nothing starchy about us.
You wore suits rather than laboratory jackets when you were listening to these [lectures]?
Oh, yes. We wore laboratory jackets, if we had one, in the laboratory, and especially if we did surgical operations on animals which we had to do in Physiology and in Pharmacology. What I’ve been describing is simply the course – the coursework. His laboratory is quite another thing – I mean his own personal laboratory.
Can you describe it?
You bet. I certainly can, because I was in the midst of it and saw it develop. Herbert Gasser, who became a very, very close friend of mine – Herbert had come back from several years’ stay in England and had become very proficient in pharmacological physiology. He was head of Pharmacology and I took that course and know how he taught; he was a perfectionist. But he and Dr. Erlanger and, I suppose, George Bishop, all agreed that the important thing to do for the sake of neurophysiology, was to develop an instrument that would be capable of following with temporal and voltage precision and fidelity, the action wave – the so-called nerve impulse. Up to that time they had galvanometers of one sort or another, string galvanometer in the end and so on, but none of them could possible follow with fidelity a thing that happened in a ten-thousandth of a second. It just didn’t move that fast.
So they were committed, these three people. But it was Herbert Gasser who started it and he knew how the Braun tube, (spells) B-r-a-u-n – the Braun tube was the original German Braun who started and first made what we now call the oscilloscope tube, like a TV tube. And so Herbert actually made one, but Western Electric had just started to make the same kind of thing. And they used to buy the Western Electric tube, which did all they needed to, except that it had a very small lifetime. And if you put it at 300 volts on the plate, then the image was rather faint and you had to be in an utterly dark room. And even then, you had to put the film right directly on the face of the tube. And then, you had to have an instrument which would cause the nerve to be stimulated and swept across the tube precisely in the same way for twenty or fifty times consecutively because it took that much to expose, to get something that made an impression on the film.
And this would be for one expose or a series of exposures?
You see, there was a German mechanician in the department who constructed a rotary device which had brushes on it which synchronized the spreading of the beam across the tube with the firing of the action potential, with the electrical stimulation, and that caused a wave to appear on the oscilloscope tube. Now they had to have, at least, anywhere from 20 to 30 of such sweeps to have enough image intensity to affect the plate at 300 volts, plate voltage. However, if you put it up to 450 [volts], which was the maximum, then it was much brighter. And you might even get a single sweep to record, but the tube didn’t last very long, and those tubes cost 125 dollars apiece back there in 1924 or so.
I understand they leased them.
No. You couldn’t lease them.
Obviously, they would just expend the entire tube.
The point is that the three of them did this together: Bishop, Erlanger and Gasser. Erlanger did all the dissection – he was fantastically good at dissecting nerves and things like that. Gasser was more or less the mastermind of it.
Was dissection necessary for these early oscillographic—?
Oh, yes. Well, the nerve had to be dissected from the animal. Like a motor root or a sensory root from the spinal cord of a bullfrog.
It wasn’t simply a matter of hooking the electrodes up to the skin of an animal?
No. The electrode would have to be on the nerve itself.
Was this a matter of it being so primitive?
No. Because, let us say that you wanted to measure the potential going down the ulnar nerve, which is on the inside of the arm coming from the brachial plexus. Going right along the wrist, here is the ulnar nerve. And if you put an electrode directly on the skin with very high gain, you might record the action potential. But it would have gone through all manner of resistance, of the tissue in between; the capacity would have changed the shape of the wave and all that. So you have to have intimate relationship with the nerve.
The point I wanted to make was that in those days one did not have vacuum tubes that had any kind of stability. They were very microphonic and low gain. As I remember it, it was a six-stage amplifier – five- or six- stage amplifier – and the gain per stage, the so-called new(?) factor, was only six-fold per stage. Therefore you had to have so many stages, one on top of the other, to take an action potential which is something of the order of anywhere from twenty to fifty millivolts, and boost it and amplify it to a point that you could put it on the oscilloscope and move that electron beam on the oscilloscope. That would take a volt per millimeter or something like that. That means you really have to amplify several thousands of times. Now, that was so microphonic that the whole amplifier was in a feather bed.
There was a biochemist in those days – Eddie [Edward Staunton] West, Dr. West, – who was a Virginian and as such liked to shoot. So he had made a shooting range right downstairs there. To the great annoyance of these three investigators, particularly Dr. Erlanger, Eddie West would bang off with that thing, which would throw everything off. (Laughs)
Did they eventually work out a modus vivendi where Dr. West had to—
Sure, sure, sure. Well, it was a standing joke. Anyway, it was extremely primitive. The place was a fairly large room, about half the size of the room we’re in.
Let me show you a photograph – is this of the period?
That is indeed. No, not quite, but very near.
This would be a later [period].
Yes, this is a later thing.
Later in the ’20s, would you say?
Oh, yes. You see, that oscilloscope was not the kind of thing that we had. And all this— No, no.
That’s [an] amplifier. We’re pointing now to a picture in the archives of Dr. Erlanger before a later development of the—
What happened was that the three of them worked closely together in this one room. Even this [room portrayed in the photograph produced by Paul Anderson] is still a room full of wires and so on. But that one [the earlier laboratory] that room, the whole thing was devoted to just that. There was a little stand there where an animal might be, or something like that; the rest is all equipment.
What kinds of animals were used for the experiments?
Rabbits; bullfrogs a great deal for motor root preparations. If they wanted to know what— The Nobel Prize they got was for describing the characteristics of – that is, Erlanger and Gasser [won the Nobel Prize] – the characteristics of different kinds of nerve fibers. They found that the velocity of propagation was a function, more or less a direct function, of the diameter of the nerve, also depending on the degree of myelination. If it were a myelinated nerve it went very much faster than if were an unmyelinated [amyelinated]. But a myelinated nerve is usually a pretty big nerve, going all the way from two or three microns in diameter to twenty-five or something like that. So, by taking an action spectrum, as it were, namely, arranging so that all the different waves – alpha, beta, gamma, delta waves – of a myelinated nerve were recorded, one could then say that the velocity of propagation of a nerve of the so-and-so diameter. They took the very nerve that they were using and had records of and sectioned it and spent many, many hours and even days – I can see Herbert Gasser still doing it – measuring the diameters of all these fibers and then plotting all that out and showing the relationship. And it was a clear-cut relationship.
Did they have difficulty measuring, considering the development of microscopes at the time? This was pre-electron microscopy.
No. No. No difficulty at all, because they were talking about a division into essentially two groups; one was myelinated and the other was unmyelinated. They had come to [a] firm conclusion that there were four distinct waves in a myelinated nerve: alpha, beta, gamma and delta, depending on the size. And that would go down to relatively small myelinated.
But then there was a discovery. By that time Bishop had left. After the success, then each one split up and had their own [unit]. Gasser had his unit, Erlanger his and Bishop had his. And Erlanger and Bishop [ed. note: Dr. Schmitt may have meant Gasser] continued to work together and knew what each other were doing. Whereas Bishop worked quite on his own. He worked with another postdoctoral student for a while, who then joined the staff, by the name of Peter Heinbecker. And those two were working quite on their own. And that ran – that caused a great deal of trouble. Because it turned out that unmyelinated fibers— In other words, very finely myelinated fibers have a different wave shape than all this alpha, beta, gamma thing. In the end, both groups put together the alpha, beta, gamma, delta and called that the A-wave. Then they found the B-wave which had B-1, B-2, and so on. These were very finely myelinated, like a diameter of one micron or two microns. Then the C-wave was very slow and that was unmyelinated, strictly unmyelinated; very small fibers.
Was it not the case that Dr. Bishop was working with ocular nerves by the time he left?
No. He was working on the saphenous nerve. As it happened, he was working on a nerve – whether he did that by plan by happenstance I don’t know and I’d just as soon not talk about it – but it just so happened that both groups came upon – let’s use that word – the fact that the original description was very partial. It had to do only with the larger fibers. It gave a valid linear relationship in that group, but when you got to the finer fibers yet, into the B and finally the C fibers group, [these had] very slow waves, centimeters per second instead of 100 meters per second. And, as it happens, the kinds of fibers that come in the cerebral cortex, we’re all very interested in those fibers there, many of the most important nerves in the brain are those little fibers – a tenth of a micron fibers – that’s a thousand angstrom units. So, anyhow, when it was all finally resolved, that’s how it turned out.
Weren’t there also some personality differences that augmented these?
Terrible, terrible, yes. I just hate to talk about it because they were all such good friends of mine. I might, however, just throw this in: Dr. Erlanger would not talk to Dr. Bishop and Dr. Gasser finally did, indeed, shake hands with George Bishop. I don’t think that Dr. Erlanger would do so. When I came back from Europe in 1929 out at the [Washington] University, I started a thing which got to be known as the Verein, (spells) V-e-r-e-i-n. They called it the “Schmitty Verein.” I was the cub of the outfit and therefore I could do anything. I could command anybody like Erlanger – any department head – and they all came out. I asked them to come and talk and just tell us what they were doing. It was a multidisciplinary group – we had Frank Bubb in mathematics and [Arthur Llewelyn] Hughes, head of physics, and biochemistry – Philip Shaffer – and Erlanger and Gasser. I invited them all, and for the first time at one of meetings, Dr. Erlanger and Dr. Bishop met in a neutral corner and they agreed to forget this thing. It’s the first time that they met and did that. Herbert Gasser of course, had in a way, made his peace with him [Bishop] before. But it was very, very awkward and George Bishop was very unlikely to want to bend in the least.
Did he feel, in the end, that he was cheated in the award of the Nobel Prize?
He was not a technician. In a sense he was treated as a kind of technician. He was, to some extent, more technical by far, certainly, than Gasser.
His own brother called him “an excellent carpenter and mechanic.”
Of course, he’s a lot more than that. But, I have long since learned that honors and awards are in some ways a snare and a delusion. For every person who is given a prize like that there are at least eight or ten who equally deserve it. In this case, all that did was to cause dissension in what previously was a wonderfully working group.
They had already, though, parted ways long before the Nobel Committee— And it was to some degree a matter of who reported to whom.
Sure. Well, Bishop got out of the department, actually.
It’s interesting, though, because people think and they want to know the truth.
I would like to talk, if I may, about Dr. Erlanger.
Yes, please.
I might, however, go on with your original question about what I did in the laboratories and so on. Having my own laboratory, I did all kinds of experiments on all kinds of subjects. And it was my aim to learn a lot about different subjects. We had an excellent bacteriologist – no, not bacteriologist. It was Arthur Isaac Kendall. He came down from Chicago and stayed with us here at Washington University only a certain number of years. But at any rate, he was an excellent kind of a cross between a pharmacologist and a pathologist.
He asked me to help him, which I did, and we published several papers together during that period when I was in my first year, I guess. I knew how to record things like the contraction of a guinea pig ileum or something like that. So I set up an apparatus in which I would record the contraction of whatever it was – the gut or the uterus or whatever – and it was in a so-called Trendelenburg apparatus. Which means it’s a little vial with a balanced salt solution and the tissue is in that. Then I hooked it up with a recording lever and Dr. Kendall dropped into that reservoir some of the most awful things – botulinus toxin, gas bacillus toxin, all very, very dangerous things. And of all things, he sucked up in a pipette this stuff from the brew where he had prepared it. I said to him, “Dr. Kendall, suppose that you just happen to suck it up in your mouth?” And he said, “Well, it has been done, but it certainly is not something to do purposely.” So I learned a lot from Dr. Kendall of a kind that I never would have learned otherwise. It was just the adventure of doing something different that I liked to do.
However, what I did do to a considerable extent, was kidney function research with Harvey Lester White. When I came down [to the medical school] I had come from the University zoology department where I’d done a whole lot. I had published two papers before I came as an undergraduate on the structure of cilia. Therefore I had a lot of histological preparations. And Dr. White told me how people were now pipetting glomerular urine, that is to say, the fluid from the glomerulus of a frog kidney. And this was done by the professor at Pennsylvania and shown at an international congress. He told me about that and I said, “For goodness’ sake, why do you use a frog for that? Look here!” And I got out some of my kit and showed him a section of node(?) necturus kidney – just held it up, not even looking at it in a microscope. And there, along the renal artery, were glomeruli like portholes in a ship, you know, right on the renal artery and great big things a millimeter in diameter. So, we got working together on necturi and got so that we could insert the apparatus, the needle or the tubule. We could then pipette that into another capillary tube into which we would subsequently then pipette the reagent in order to determine the concentration, etc., etc. So we worked together on kidney function and published several papers.
And then I, as a youngster yet, decided to demonstrate this at the International Physiological Congress in Stockholm in 1926. I must say that my father – when I look back at it – he certainly helped me in many, many ways, though he knew nothing about such matters. And he allowed me to go; I had to pay my own way, of course. So, it’s a long story, but I tried to get the necturi – mud puppies – at the Finger Lakes in Ithaca. When I got up there, my young lady, whom I married shortly afterwards, met me in New York. I went up on the train to Ithaca where the fellow there was catching necturi. He said he’d have an appropriate bucket all prepared and a dozen animals. When I got there, he had three bedraggled-looking necturi; it was terribly hot, and no container at all. So we put what I had in the bathtub of the where ever it was, the pension where we were staying in New York – she in her place and I in mine. In the morning they were all dead.
But fortunately while I was in Ithaca I had the presence of mind to call at the Battery, which is no longer there, of course. They had a marine aquarium, and she and I, while we were strolling around in New York before I made the trip, went into the museum and there we saw nectura. So I went around and spoke to the director, who was a woman, and asked how she kept them and all that and that I worked on them, etc. When I found what horrible stuff I got in Ithaca, I got on the phone to that lady and she said, “Call me back in fifteen minutes.” Which I did. She said, “I can give you two good, live necturi, and if you want [them] I can give you two cryptobranchae.” Now, cryptobranchus, as the word suggests, has hidden gills, not fluttering gills out waving in the fluid. But they also had pretty good kidneys; the glomeruli were not in a line but they were all right. So she arranged that I should come with a big pail and I could get it early in the morning because my ship left for Europe at noon. I went to a hardware store and got two big buckets and got them – the fellow [at the museum] had orders and he got them out for me.
I went on the Helig Olav, which is a ten thousand ton ship and it was the hottest day in the history of the weather bureau in New York, which was some ninety years [old by] that day. Within one day, all those necturae [ed. note: Dr. Schmitt may have meant the cryptobranchae] were dead. And I was terribly sad. But the necturae were not [dead]. So the passengers got to knowing one as “Helig” and the other one was “Olav.” (Laughs) And they lived on. So I gave the demonstration; I kept them right with me no matter where I was. In Norway, the captain of the ship took us up to the top of the _____(?) and I had my animals right with me. The railroad went from Norway to Sweden.
Oslo?
It was not Oslo at that time. It was—
The name of the city? Christiania?
Christiania, right. At any rate, at the border – at midnight, it was – at the border, I was berthing with the head of the physiology department of the University of Pennsylvania. Herbert Gasser and this Dr. Meek worked together. Well, at the border, the train was boarded by the frontier guard. They saw these animals and they couldn’t think of any reason why they should allow such animals into Sweden. Fortunately, I thought quickly and showed them a gilded diploma – certificate. Well, the certificate happened to say that I was permitted to take the micro-dissection _____(?). It had nothing to do with the animals, but they couldn’t read English and so I got the animals in.
At any rate, to make a long story short – the demonstration was made. I shouldn’t go into all this.
Oh, no. It’s a delightful story.
Herbert Gasser was supposed to help me, because it was difficult to do the operation. You’d have to anesthetize the animal, put him down on the board and do the operation without loss of blood. I started on my own, when a kindly gentleman came in and helped me. Together we made the preparation work and I said to him, “I’m sorry I didn’t introduce myself. My name is Francis Schmitt.” And he said, “My name is Rudolf Höber.” Well, I almost fainted, (spells) H-o-umlaut-b-e-r – he was the dean of all physiologists. He was the teacher of [Otto Heinrich] Warburg and [Otto Fritz] Meyerhof. We read his book – it was our bible – in German. [Dr. Schmitt gives the title of the book in German] – The Physical Chemistry of Cells and Tissues. I almost fainted, that the great Höber had helped me! Years later he came and talked to me about that same incident.
At any rate, it worked and some of the top physiologists of the world were there. Dr. Starling, who was the top man in England, a kidney specialist, saw it and was so taken by it that he himself did it – took necturae to experiment on the next year himself. So, for a young person in 1926 – I was twenty-two – it was quite an experience because I met so many famous people. This, to me, was one of the great opportunities of my life. I’ve been to many of those congresses and to meet these people, not simply because they’re great men, but to meet them under circumstances [where] you really got to know them. And that happened so often in my case and meant all the difference to me.
At any rate, so I came back. Now that was all, in a sense, by the wayside. I had been doing my medical student work; I had been publishing the kidney stuff with Dr. White. So finally, both Dr. White and Dr. Bishop said, “Look, you’d better go to the boss and ask what should be your thesis. After all, you know, you’ve got to have a thesis to get a degree.” So I went and Dr. Erlanger thought about it and then he said, “I think it would be nice if you would work on the irritability, excitability of heart muscle.” It just floored me because every great physiologist for a hundred years had worked on that field. What on earth was a person—
He himself.
Of course. Well, I wanted to be married and to get married required that I have my degree. So, I was under very, very great stress in that last year. I used big turtles and cut the ventricle of the turtle – ventricular strips off the ventricle – so that the strip might be ten centimeters long. And I arranged to pass the muscle through a series of vessels, two outside ones and three inner, smaller ones, with a rubber dam between each one through which I strung the muscle so that the fluid that was in one vessel would not mix with that in the other. The idea was to change the ions – what type of ions and what concentration of ions – and to see whether the ionic strength and the kind of ion made a difference on the action potential.
Well, I did one experiment after another. There was a rod, a very, very light rod which connected to a recording lever on each one of those five segments. So there were five records that had to be analyzed. Then, [also] a timing record and another record which said when I did something to it. Those all had to be analyzed, which I did at night, after supper. That was really hard work and I getting nowhere, really nowhere. It was very disheartening. And this one day, I had worked all day on it and getting nothing that I could see was unusual. When Dr. Erlanger, as was usual, came at four o’clock and suggested horseshoes. I didn’t see what I had to lose and we went out and played horseshoes.
When I came back, just for luck, I pressed the key again, stimulated it, and the impulse went to the first barrier and I thought it was a complete block, but it wasn’t because the impulse went through after a great length of about a full-second delay. And having gone through, of course it set up the train which went on down to the other parts of the equipment, making each contract in turn. But then, it fired back on the initial segment and we gave that a Greek name, which was opisthodromia, which means to fire, to conduct (dromio means to conduct and opistho is to return). That was opisthodromia. And I asked Dr. Erlanger in – he came in and he saw it and it did it again. He said, “If I were you, I’d stay up all night and get all the data you can. I don’t think you’ll ever see that again – it’s a very important observation.” So I did. But then I learned, in the end, what it was. The asymmetry was not just the ionic differences, but rather a combination of pressure from that rubber dam, which was doing damage to the tissue, as well as the imbalance of ions. To make a long story short, I got a whole series of experiments.
How were you recording them?
All on a moving smoke drum, and that had to be shellacked and then analyzed. So, it was very exciting and I developed a theory according to which – and I could show it in a diagram much easier than talk about it – if the impulse in one part of the heart were going to the ventricle, as indeed it does, and if that section divided into a “Y” the impulse would go down both ends of the “Y” to the heart muscle. But, en route, on one arm of the “Y” there was a lesion. And there it was not total block, but rather, what I call monodromia – which means it conducted in one direction, primarily, rather than in both directions. But the other arm of the “Y” had gone beautifully through; had excited the heart muscle. Now the heart muscle, in turn, spread its potential, which fired up into that part of the “Y” that didn’t function and made it function and it went through. And having gone through, it went back on the other segment. It was a re-entrant phenomenon. And you had the essence of fibrillation. So this turned out to be a model of cardiac fibrillation, and with very good explanation of the whole thing.
I wrote it up and it was published in the American Journal of Physiology for 1928. I wrote it up in California after I was married. Almost every year, and indeed even last year (that’s 1981), I got and continue to get requests for permission to use Figure 3 (I think it is) and Figure 5 and to reproduce it. That’s over fifty years after it was published – I have never looked at the heart muscle again, and I have never had such requests from anything else that I have ever published. And here it all came about from horseshoes.
If I were to look in the science citation index I would probably still see some references. Just briefly, you mentioned the horseshoes. This was Dr. Erlanger’s favorite sport?
Well, George Bishop and Eddie West and I did it. We worked hard and created two horseshoe courts with sand and enclosures and so on. The pegs were running parallel with the building that connected the old South and North buildings.
The old refectory building?
Yes. It was parallel to that, in other words, parallel to Euclid. And I got two headlights from my father’s old cars and put it on the fourth-floor seminar room so that at night we could play horseshoes after a meeting; just turn on the lights. And we were nuts about horseshoes. We had been playing for some years. As a matter of fact, clinicians used to come across the street from the clinic and they would clean us out. They were very good horseshoe players; they were better than we were. We had a lot of fun, and then Dr. Erlanger got into it.
I might say as another little anecdote: I had to take an examination, of course. The thesis was finally finished, and on time; submitted to the graduate school just about on time. I was something of a nervous wreck trying to get it all done. And Dr. Erlanger corrected everything. As I produced sections he would take it home and correct it and in the morning bring it in and my spirits sunk every time I saw what it looked like. It was all scratched up, and I would ask Miss Stubinger [who] was his secretary – I would ask Dr. Erlanger, “I’m sorry, I don’t understand. What is this that you’ve written?” He’d look at it and in some instances he couldn’t read it, so Miss Stubinger could, and she could read it. He was so good about it, but he was such a perfectionist. I learned how to write scientific documents from Dr. Erlanger. It was starchy, to be sure, but precise. And finally mine got written to his satisfaction.
So we had to go out to the campus for the examination. I was warned by Bishop. He said, “You’ve been pretty cocky and we’re going to take it out on you today.” And they did. The examination went on for two hours or more and it was a very large board. I did, I thought, reasonably well, but the last question that was asked was by Dr. Shaffer, head of biochemistry. He said, “Mr. Lindbergh has been over the ocean now for over thirty hours. Would you tell this board the physiological and biochemical processes by which he manages to keep awake?” If I had wanted to be rude, I would have said, “Look, I’m fighting like that myself.” (Laughs) But I managed to say something which I’m sure wasn’t very good, but the ordeal was finally over. And going back, of course, it was [a] celebration because it was over – the damn thing was done. So we went and played horseshoes. We were busy playing horseshoes when somebody rushed out of the North Building and said, “Lindbergh has landed in Paris.” So I know when I finished my exam.
Everybody knew that the flight was in process?
Oh, sure. You bet – the Spirit of St. Louis.
What sort of man was Shaffer?
Shaffer was professor of Biochemistry and an excellent biochemist, who got into the insulin game very early. He was a carbohydrate chemist. He very early got into the question of insulin – and there were big discussions. I remember very well that at one of the discussions – big open seminars for the public – my professor at the University, Dr. Caswell Grave, being something of a philosopher, asked the question, “If it’s true that these people with diabetes are going to be saved by your injections of insulin, they will have children, their children will have children and they’re all going to be diabetic. Now is that a good thing to do or isn’t it?” Of course, everybody knew the answer: it’s the only thing you can do. Dr. Shaffer was a very close friend of mine and he helped me on many occasions, as did Dr. Gasser, who was head of Pharmacology.
So you got along equally well with Dr. Gasser?
Oh, very well indeed. My wife, whom I was to marry, was an excellent pianist. When we came back from our second postdoctoral year in Berlin in 1929, [and] settled down out at the University, I as an assistant professor, she bought his piano, which was a beautiful Steinway reproducing grand – Aeolian reproducing grand. You could buy records, and many times he had parties – he called them Roman parties because everybody roamed around at his apartment. He did a pharmacological experiment on my wife – [he] had her play the Minute Waltz – and she used to play, I think, faster than probably she ought to. But she was a very good pianist. Then he clocked it. Then he asked her to please take a Martini, which she did. In those days we weren’t quite that used to cocktails. And then she played it again.
That may not have been legal, as a matter of fact.
(Laughs) Yes, you’re right.
The Volstead Act had not been repealed. (Laughter)
That’s right, that’s right. The interns and residents used to come and pinch alcohol from [Ethel] Ronzoni, who was Mrs. [George] Bishop. She ran the service lab in biochemistry and she had alcohol. So she put ipecac in it for the devil of it and it wasn’t so pleasant for them.
It’s interesting that you’ve mentioned Dr. White. What sort of person was he?
He was a man who was a pragmatist; a person who thought very deeply. He read Greek and Latin, to a degree. He was very interested in formal philosophy. He tried to reason things out and by “reasoning things out” I don’t mean just physiologically. I mean all kinds of social matters and so on. In many ways he was a very fine person in that regard. We worked together very closely; we went to demonstrate the kidney function in necturus on a very bitter cold winter [day] in my little two-seater car. Well, it’s a long story. The animals almost froze in the back of the car; we had to take them inside the car or they’d be dead – just frozen. It took a long time. In Ohio in those days, there were crosses where any fatal accident happened. It started to snow, snow heavily, so we got to betting when we saw a bad hill or something how many crosses would be at the bottom. The chances are that we were looking more for crosses and all that at the side of the road than watching our business. But we managed to get through.
You were headed to Columbus?
To Cleveland. We made it to Columbus and stopped [for] the night – there was no sense going on. At any rate, he had a brew of some kind – it was some very potent – like gin, I guess, something like that. I never drank that kind of stuff myself, but he had it in the back of the car. And I drank it with him because it was cold. (Laughs) He and I were on many expeditions.
Well, Harvey Lester worked together with me on more than science. In the end, of course, he took over as head of the department [of Physiology]. I was offered that job but I had already gone to MIT and did not feel— To succeed Dr. Erlanger would have been a great pleasure and a privilege, but I just had it so well in Boston that I couldn’t possibly consider it. Harvey took it and became head of the department.
How about Carl Cori? You wrote at least one publication with him.
Oh, yes, sure. Carl’s now eighty-five, you know, and still reasonably—
You’re in contact with him?
Oh, yes – he and Gerty Cori. You bet. I was working on nerve, of course, and wanted to know when one stimulated nerve whether lactic acid increased or not under conditions of anaerobiosis, which means removal of all oxygen, or put the nerve in carbon monoxide, which I learned from Professor Warburg in Berlin. And I worked with Gasser on the same subject, using carbon monoxide – 98 percent carbon monoxide plus 2 percent oxygen. In that case, the nerve would fail, fail to conduct and the curve of excitability would go down slowly to zero. And then, without changing the partial pressure of the carbon monoxide or anything else, you simply illuminated the nerve. Dr. Warburg had gotten the Nobel Prize for using that technique, because he had proved that when you illuminate the binding capacity of the oxygen for the biocatalyst was much less in the presence of light than it was in the dark. So without changing anything, the action transfer came right back. And we followed it – you turn off the light and you, in a sense, turned off the excitability and the curve plummeted again to zero. And Gasser and I published two papers on that. We worked together on it. This would have been in the early ’30s.
I worked also with Helen Graham on the same kind of thing, but with Carl Cori to find out if there were lactic acid produced under these conditions. He found that there was not.
So you set up the conditions of the experiment and then he did the analysis?
Yes. He did the analysis, which is a pretty high-powered analyst, I’d say.
You’ve alluded to Helen Graham. How was she to work with?
Just great. What happened was that we were working on what were called “slow potentials.” We had found that if, instead of using [an] oscilloscope to measure relatively fast potentials as they moved from one part of the body to another, instead of that, if you measure the slow change of polarization of the nerve membrane – by “slow,” I’m not talking about milliseconds or even seconds – I’m talking about minutes and hours. And if one had what was called a really good non-polarizable electrode, so that the electrode at least didn’t cause polarization changes, one could follow the change of potential by balancing the potential in an apparatus – a voltage diviner – and keeping the oscilloscope at zero. As the potential changed that would move from the point in the middle of the tube and you would balance it and measure the voltage. In that way, we measured potentials that lasted for hours, steady potentials, and those were potentials that I discovered were oxidated in nature. That is to say, they involved oxidated processes. Whereas fast potentials were much, much more efficient than— So, she and I worked together on a number of those things, and very cordially, indeed. She smoked, of course, very much.
Let me throw in another name: Viktor Hamburger.
Oh, Viktor. Viktor, you see, came on – he escaped from Germany. He was a student of the Nobel laureate in that field in Germany.
Hans Spemann.
Hans Spemann. He came to Canada first. He came to our lab from Canada and was the junior assistant professor. I was junior assistant professor till he came. And then I went up in the ranks and so did he. Dr. Grave, the head of the department – from Hopkins, or course – set aside every Thursday night for what he called “philosophical discussions.” He was used to that from Johns Hopkins. All the graduate students participated and all the staff, and they had to be there at seven o’clock – or seven thirty, I think it was seven. And Dr. Grave was the master of ceremonies and somebody was told off to read. We started a book of some sort and it was usually a very provocative book. So somebody, a graduate student or a staff member, and he reported on it. Then there was general discussion and in this general discussion there was [disagreement]. It was during these discussions that Viktor and I went at each other. He was not a physiologist, nor a chemist, but he was an excellent biologist and an excellent student of growth and development, which I knew very little about. So, we were very, very friendly, but we certainly had some pretty animated discussions. It went on like that until when Dr. Grave retired – I took over and Viktor then handled all that part of the curriculum. And then after I left, of course, he took over. And I’m happy to say that an F. O. Schmitt lecture series was begun at MIT some six or eight years ago, ten years ago, and Viktor gave one of those lectures. It was just marvelous – it was great.
I was out there – our meetings are right across from the campus there, but of course he wasn’t around and whether I’ll get to see him this time I don’t know. But he’s still excellent; in good condition.
You returned to St. Louis just in time for the Depression, and being a researcher, needing money for experiments, were there really great problems?
You bet. There certainly were.
Can you describe the problems that you encountered?
Yes. The question was – what kind of work shall I do? I obviously couldn’t do oscilloscopic work; I had no expensive equipment of that sort, nor did I, at the moment at least, want to do that. But I did want to do respiratory work of the kind that I’d learned from Meyerhof and Warburg and do work on nerve respiration and the metabolism of nerve. Dr. Ronzoni was good enough – Mrs. Bishop – to lend me some of her equipment. My brother, who was ten years younger than I, helped in making the apparatus work, and he invented a tube later on for a thermostat and kept everything going. So we got working on it doing the effect of carbon monoxide on nerves. It turned out that if you put carbon monoxide on them and then illuminate them in the bath, while they’re shaking in the thermostat bath, while you’re reading the manometer, the respiration comes back, does indeed just like the action potential did, etc.
Now, I started in that kind of thing. However, I learned the value of a technician when I was in Germany. A good technician is a wonderful thing to have. It was just at this time that the man who later became vice-president of the Rockefeller Foundation for medicine, Warren Weaver, came through and saw what I was doing and gave me a grant from the Rockefeller Foundation for ten thousand dollars. That made it possible for me to hire a technician. It made it possible for me to do a number of other things which you wouldn’t believe, but things were so cheap in those days. So that’s what really set me up – was that ten thousand. I’ve told Warren Weaver many times during his life how much that meant to me.
How long did that last?
Well, the technician stayed on more or less indefinite. He was there even when I left. And we got funds after that – we succeeded in getting funds because I had been publishing research.
What kind of other sources were available?
Well, the Rockefeller Foundation itself continued and indeed then later when I went to MIT, they gave (what was it?) seventy-five thousand dollars to buy the first electron microscope in this country. And I was to find out what there was to electron microscopy. We had the first electron microscope in this country, when I went to MIT – and that was Rockefeller. But that was a special grant. They gave us a half million dollars on one occasion and supported our work in general – and he [Warren Weaver] had got used to supporting the work.
The federal government hadn’t entered the picture at this time.
No. Hadn’t started [yet].
During the ’30s you did experimentation with applied x-ray diffraction and polarization.
Exactly. Yes, exactly. I can tell you something very graphic. It’s this – that in 1923 – I was still an undergraduate – I went to the Marine Biological Laboratory in the summer. They gave summer courses.
This was at Woods Hole [Massachusetts]?
At Woods Hole. The department awarded me a fellowship for that purpose. But there was only seventy-five dollars available and then Dr. Hansen had his candidate. So they split it – so I got thirty-seven dollars and so did his candidate get thirty-seven dollars, to go to Woods Hole for six weeks. And it happens [that] I went on for another two weeks with Robert Chambers. So my father, of course, was asked to support this venture, which he did.
At Woods Hole I witnessed what I like to refer to as the battle of the giants, because Thomas Hunt Morgan, who after all gave the name “gene” and who got the Nobel Prize for his work on drosophila genes, which are banded – chromosomes are banded. He showed – he set out the gene map, with relation to particular bands, knowing that one gene was associated with this band or that or the other. All his gang was there – Sturtevant and Bridges and so on. They had – I’ll never forget it – a debate, in a sense, in an old wooden lecture hall at Woods Hole in the evening. Morgan and E. B. Wilson, the top cytologist of the day, [Clarence Erwin] McClung and one or two others – McClung, of course, was a great developmental biologist. They, on the one hand being morphologically and genetically oriented and a man by the name of Jacques Loeb on the other hand.
A brother to Leo Loeb?
Yes. Leo was not a physiologist/biochemist like Jacques was. At any rate, he had a little shack close to the eel pond. I went in as a young student – I was nineteen at the time – watched him doing experiments measuring the osmotic pressure of proteins. And he proved that this old gag about colloids – and everybody ascribed living things to this strange colloidal state which did magical things – he made it clear in a book that he wrote then on the basis of that work at Woods Hole of what’s called the colligative properties of solutions which says that the osmotic pressure – and it turns out a number of other properties like that – is proportional to the number of molecules there and not to the size of them. In other words, a protein may have a thousand formal charges, positive or negative. But it’s still an electrolyte, like salt is, like sodium chloride, and nothing magic about it.
He turned to these people who were talking about the gene; you see, if you know the length of a chromosome in which there are a certain number of genes, you divide one by the other and you get the average size of a gene, which turned out to be about a hundred angstroms and their view was that it was some little ball, a string of little balls like that. I talked to Bridges, actually, and Bridges said, “You see, they’re cross-striated, like muscle.” He wondered whether maybe the structure would be like muscle. It happened that I knew a lot about muscle – I’d worked on it a good deal. I assured him that I didn’t think it was like muscle at all. In other words, they were pretty naive about chemical matters, these people. It was clear to Jacques Loeb that you’d never advance the field, literally, by the kind of formalisms that they were indulging in. You would advance the field of genetics, indeed as they did, and probably developmental biology and certainly morphology, but not a real knowledge of an understanding of what’s going on.
In other words, this was my awakening – at Woods Hole – because it was clear to me that you must know how to describe things. The important things that you need to know are at the molecular level – that was the point. I became, in short, a molecular biologist. I was awakened to all kinds of things – in Merkel Jacobs’ class in physiology, for the first time I heard of an electron as being involved in oxidation reduction reactions. I knew they chased around in iron wires, but I didn’t know that they— The whole world was opening up.
And this, to repeat, was while you were an undergraduate.
Yes, I was a junior – just at the end of my junior year. We were supposed to be graduate students, but I got in.
And this was applied to your thinking much later?
Right. I became a molecular biologist, in a sense, right then and there. As such, to deal with molecules, I began really trying to see how one would do it. And it was clear, one hadn’t the slightest notion of any electron microscope at all in those days. And one knew that the limit of resolution of a microscope using light was one-half the wave length of that light, which would mean that the smallest thing you could ever really see would be about fifteen hundred angstroms in diameter. Which is, of course, not molecular at all.
It turned out, I read a book by a German by the name of Schmidt (with a d-t) – W. J. Schmidt. It’s called [gives title in German] which means The Structure of Animal Tissues Analyzed by Polarized Light. He knew his optics. I read that book very carefully, and then [also] the book he published subsequently in 1937. And, in short, I knew how to analyze structure by use of polarized light. And a French paper had appeared also which gave fancy names to it; like _____(?) and _____(?) and so on. Fluid crystals – I learned about fluid crystals, also.
In short, the molecular biology when I came to the medical school – I had knowledge about those things. In fact, I gave a triple department seminar, just arrived as a young student, and talked about the field, which nobody understood at all, of course, because it was a specialty. The whole field of polarization optics, and then x-ray diffraction. By x-ray diffraction – I was determined that I should do x-ray diffraction. Indeed, coming to this medical school, to a degree – of course it was Erlanger that attracted me – but also another thing that attracted me was the willingness of Sherwood Moore, who was head of radiology, to let me have an x-ray tube. And he let me have a place where I could work on it. And I did indeed set up a diffraction outfit down there and I got diffraction patterns of salt, but indeed that’s all I could do because this was a tungsten tube, like a therapy tube, with a wave length of 0.2 angstrom [unit] – very much shorter than I needed. I needed a copper tube with a wave length of about one and a half angstroms. What Moore gave me helped not a bit, but it decided that I’d come to this medical school. Because the University of Pennsylvania – Dr. Merkel Jacobs who was head of the thing at Woods Hole, had singled me out in a way and I guess he had convinced them at Penn to offer me a very good fellowship of twelve hundred dollars a year – which in those days for a young guy was really very good. I turned it down to stay here.
Your investigation of the x-rays was deferred?
It had to be, until later then, when I was back out here in the University as an associate professor I guess, or something like that. And then, I got really going into it. Since I had no tube, I made regular trips to Urbana where Dr. Clark had a good x-ray diffraction unit – a copper tube. And I went on Friday, complete with animals – frogs, cats, lobsters, and stayed till Sunday night getting x-ray patterns. And then Dr. Richard Baer, who went along with me to MIT then, got into it also, and we did x-ray diffraction together. And I learned x-ray diffraction as he did, together. And we developed what is called small-angle diffraction. That means to say that we could detect very large repeating periods. You see, the distance between atoms as in water is about one angstrom unit. And we found a diffraction of 171 angstroms in the radial direction in the nerve myelin. That was a big spacing, and together with polarization optical analysis, we were able to derive an understanding of the structure and orientation of the molecules of that myelin. And that turned out to be a model of all cell membranes. Because that’s what myelin proved to be.
One of my students, Dr. Guerin(?) at MIT, discovered the so-called wrap-around theory of myelin, which is correct. And so, then, after all these trips, we’d take enough pictures that when we came home it would take us another month or more to analyze them, [and then] we’d go on another trip and get some more data. A chap who was from Cal Tech came as a post-doc with me, really as a research associate of sorts, and he built an x-ray tube.
What was his name?
Palmer. And Dr. Palmer, very slowly, built and constructed an x-ray tube so I’d have an x-ray tube right here at Washington University.
So this would be by 1932-33?
No. It was nearer to the time when I left. It was about 1938 or ’39 and in there. We did a lot of crucial work in 1938-39 [and] published [it] in the early ’40s.
Diffraction and polarization optics was your major research interest in the ’30s?
It had to be. That’s all there was. And then came this offer for an electron microscope. And then, of course, at MIT, I got that going and Dick Baer had come along and he was set up with a small-angle x-ray equipment. I saw to it that all that was provided. And we started working in collaboration; he with x-ray diffraction and I with electron microscopy and polarization optics, when an influx of young doctors, M.D.s, primarily, joined our group as post-docs. I just came from a conference out there in which some of those post-docs—
Electron microscopy came to be an important part of the research program here.
Yes, of course.
Dr. Dempsey and others.
Sure, sure. You bet.
Just one brief question – much more recently you exchanged information or worked with Dr. Robins in Psychiatry – Eli Robins. And this involved proteins?
Oh, yes, brain proteins. Through him I got to know Moore. And Moore has discovered several proteins, one of which he calls S-100. And another one is 14 [unintelligible] – he has some very empirical names on them. But S-100 became very well known. It was thought to be nerve-specific. He came out and gave a lecture at our place in Boston. I had arranged that an excellent immunologist should be there from Brandeis. And the immunologist said, “If you will give me some of that protein, I’ll make an antiserum to it.” Which both of them did. And that antiserum went around the world very quickly; to Tokyo, to all around, Budapest. And people were able to apply an antibody to discover whether or not S-100 existed in this or that or another nerve for preparation. That’s correct. When I think back on that, it seems so incredible, because at Woods Hole we had a week-long session at Wood’s Hole last May. It was on the impact of molecular genetics on neuroscience. The book is to appear next month, called Molecular Genetic Neuroscience. There are thirty-nine speakers and chapters in it.
I am truly sorry to interrupt at this time. This is the end of our tape and the end of our interview with Dr. Francis O. Schmitt. Thank you very much, Dr. Schmitt.
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